Ovarian cancer is the leading cause of death from gynecological tumors and the fourth most frequent cause of death from cancer in women. In 2005, it is estimated that 22,220 new cases will be diagnosed and 16,210 women will die of the disease in the U.S. (American Cancer Society Facts and Figures, 2005). The high lethality of invasive epithelial ovarian cancer (ovarian cancer) is primarily due to the advanced stage at which it is typically diagnosed, when curative therapy is ineffective. Efforts at early diagnosis have been frustrated by the poor performance of screening methods. Thus, there is tremendous need for increased information about the risk factors for and underlying causes of ovarian cancer. The cause of ovarian cancer is unknown, but is thought to be multifactorial, with hormonal, genetic, and environmental factors playing a role. The most strongly established hypothesis focuses on ovulation and/or reproductive hormones and is based upon consistent epidemiological evidence and corroborative in vitro experimental results. In addition, genetic factors play a role, with increased risk in relatives of ovarian cancer patients. At present, these observations offer the most promising clues to ovarian cancer biology. An attractive hypothesis is that a significant part of the genetic risk may be due to variation in genes that influence reproductive endocrinology. We are testing the association between variation in genes involved in gonadotropin signaling and risk of ovarian cancer using samples from two completed case-controls studies. We are requesting funds here to expand the sample size of this data set by genotyping additional cases and controls from a third recently completed ovarian cancer study with the aims of (1) providing robust results of the association between variation in genes involved in gonadotropin signaling and risk of ovarian cancer, (2) exploring the relationship between variation in genes involved in gonadotropin signaling and risk of ovarian cancer by histology and environmental exposures such as oral contraceptive use, parity, and menopausal hormone therapy and (3) conducing a 'gonadotropin signaling pathway analysis' to understand the complex manner in which these gene jointly influence ovarian cancer risk. [unreadable] [unreadable] [unreadable]